Vascular Adhesion Protein-1 (VAP-1) as Predictor of Radiographic Severity in Symptomatic Knee Osteoarthritis in the New York University Cohort
Abstract
:1. Introduction
2. Results
2.1. Baseline Characteristics of the Subjects in the New York University (NYU) Cohort
2.2. Elevated SSAO/sVAP-1 Levels in Synovial Fluid of OA Patients
2.3. VAP-1 Locally Overexpressed in the Synovium and Not Cartilage of End-Stage Knee OA Patients
2.4. Serum sVAP-1 Levels Correlated with Pain
2.5. Correlation of Baseline Serum sVAP-1 Levels with Other Biomarkers
3. Discussion
4. Materials and Methods
4.1. Symptomatic Knee OA (SKOA), New York University (NYU) Patient Cohort
4.2. Synovial Fluid, Synovium, and Cartilage from Non-OA Subjects and OA Patients
4.3. Microarray Gene Expression Analysis
4.4. Cytokine and sVAP-1 Measurement
4.5. Real-Time Quantitative Polymerase Chain Reaction (qRT-PCR)
4.6. Histological and Immunohistochemical Analysis of Human Synovial Tissue and Cartilage
4.7. Statistical Analysis
4.8. Ethics Approval
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variable | Normal (N = 24) | SKOA (N = 372) | p Values | Adjusted for AGB p Values |
---|---|---|---|---|
Age (years) | 54.63 (9.37), [40.00–75.00] | 61.21 (10.51), [37.00–88.00] | 0.003 | |
Gender (%) | ||||
Male | 50% | 36.93% | ||
Female | 50% | 63.07% | ||
BMI (kg/m2) | 26.30 (3.92), [20.00–32.40] | 26.35 (3.50), [15.40–32.60] | 0.943 | 0.943 |
VAS (0–100) | 0 | 46.97 (26.47), [0.00–100.00] | NA | NA |
WOMAC (0–100) | 0 | 30.97 (24.73), [0.00–98.60] | NA | NA |
JSW (mm) | NA | 3.39 (1.34), [0.00–7.30] | NA | NA |
KL Grades | ||||
KL0 | 63.64% | 5.41% | ||
KL1 | 36.36% | 15.68% | ||
KL2 | 0.00% | 32.70% | ||
KL3 | 0.00% | 31.35% | ||
KL4 | 0.00% | 14.86% | ||
IL-1Ra (pg/mL) | 354.53 (172.28), [91.40–726.43] | 350.04 (156.37), [97.97–999.98] | 0.901 | 0.943 |
MMP-1 (pg/mL) | 2388.24 (1140.35), [1137.52–4679.16] | 3151.94 (2383.33), [401.28–17,537.19] | 0.146 | 0.351 |
MMP-3 (pg/mL) | 16,525.13 (8777.40), [6684.15–33,139.95] | 17,517.27 (16,424.86), [3768.51–244,674.57] | 0.784 | 0.943 |
MMP-9 (ng/mL) | 49,197.66 (56,813.60), [9256.92–257,706.04] | 38,409.48 (29,838.25), [9426.51–197,065.54] | 0.135 | 0.351 |
IL-15 (pg/mL) | 1.18 (0.30), [0.70–1.90] | 1.15 (0.32), [0.6–3.29] | 0.714 | 0.943 |
hsCRP (mg/L) | 4.06 (4.85), [0.14–19.85] | 2.73 (3.68), [0.00–37.00] | 0.117 | 0.351 |
CD163 (ng/mL) | 679.84 (317.42), [291.74–1852.40] | 656.09 (236.68), [164.69–1501.75] | 0.692 | 0.943 |
HA (ng/mL) | 29.59 (18.07), [1.91–72.72] | 30.20 (29.75), [0.76–193.22] | 0.929 | 0.943 |
sRAGE (ng/mL) | 1303.70 (542.76), [435.92–2463.60] | 1106.13 (571.74), [239.11–4657.23] | 0.182 | 0.363 |
sVAP-1 (ng/mL) | 569.90 (178.01), [276.32–1105.39] | 430.00 (115.50), [136.16–851.32] | <0.002 | <0.0001 |
Variable | Normal (N = 14) | SKOA (N = 301) ≥51 Years | p Values | Adjusted for AGB p Values |
---|---|---|---|---|
Age (years) | 60.79 (6.94), [51.00–75.00] | 64.69 (8.34), [51.00–88.00] | 0.086 | 0.305 |
Gender (%) | ||||
Male | 64.29% | 35.55% | ||
Female | 35.71% | 64.45% | ||
BMI (kg/m2) | 26.62 (4.08), [20.00–31.90] | 26.35 (3.52), [15.40–32.60] | 0.779 | 0.934 |
VAS (0–100) | 0 | 46.12 (25.83), [0.00–100.00] | NA | NA |
WOMAC (0–100) | 0 | 30.66 (23.25), [0.00–91.60] | NA | NA |
JSW (mm) | NA | 3.28 (1.37), [0.00–7.30] | NA | NA |
KL Grades | ||||
KL0 | 46.2% | 4.3% | ||
KL1 | 53.8% | 12.6% | ||
KL2 | 0.0% | 30.6% | ||
Kl3 | 0.0% | 34.6% | ||
KL4 | 0.0% | 17.9% | ||
IL-1Ra (pg/mL) | 362.21 (163.82), [91.40–702.70] | 363.47 (154.69), [97.97–999.98] | 0.977 | 0.977 |
MMP-1 (pg/mL) | 2511.82 (1290.26), [1137.52–4679.16] | 3230.39 (2430.58), [401.28–17,537.19] | 0.274 | 0.657 |
MMP-3 (pg/mL) | 15,704.52 (7796.96), [6684.15–33,139.95] | 17,546.72 (17,564.45), [4685.58–244,674.57] | 0.697 | 0.934 |
MMP-9 (ng/mL) | 41,278.95 (36,076.83), [9256.92–150,916.05] | 38,662.00 (28,912.33), [9426.51–184,835.39] | 0.745 | 0.934 |
IL-15 (pg/mL) | 1.28 (0.28), [0.70–1.90] | 1.14 (0.30), [0.63–3.29] | 0.102 | 0.305 |
hsCRP (mg/L) | 4.80 (5.59), [0.14–19.85] | 2.91 (3.96), [0.00–37.00] | 0.090 | 0.305 |
CD163 (ng/mL) | 749.40 (348.24), [483.96–1852.40] | 687.27 (235.73), [223.48–1501.75] | 0.396 | 0.680 |
HA (ng/mL) | 34.51 (17.67), [13.25–72.72] | 33.78 (31.59), [0.76–193.22] | 0.933 | 0.977 |
sRAGE (pg/mL) | 1342.65 (492.87), [802.28–1927.11] | 1142.09 (615.22), [293.75–4657.23] | 0.396 | 0.680 |
sVAP-1 (ng/mL) | 577.93 (192.95), [332.83–1105.39] | 437.86 (111.13), [161.94–851.32] | <0.0001 | <0.0001 |
Variable | Normal (N = 20) | OA (N = 45) | p Values | Adjusted for AGB p Values |
---|---|---|---|---|
Age (years) | 75.00 (10.72), [51.00–90.00] | 62.15 (11.47), [43.00–87.00] | <0.00001 | |
Gender (%) | ||||
Male | 66.67% | 45.83% | ||
Female | 33.33% | 54.17% | ||
BMI | NA | 28.74 (5.08), [20.00–44.09] | NA | NA |
KL Grades | ||||
KL1 | NA | 17% | ||
KL2 | NA | 26% | ||
KL3 | NA | 33% | ||
KL4 | NA | 20% | ||
KL not known | 4% | |||
IL-8 (pg/mL) | 22.38 (39.90), [3.21–134.79] | 24.68 (42.13), [1.04–249.18] | 0.839 | 0.979 |
HSIL-6 (pg/mL) | 122.62 (193.02), [0.3–496.45] | 122.22 (140.02), [5.26–630.25] | 0.993 | 0.993 |
CCL2 (pg/mL) | 682.53 (631.01), [0.10–2125.20] | 357.34 (179.17), [36.73–953.08] | 0.002 | 0.004 |
CCL4 (pg/mL) | 1.12 (4.43), [0.10–19.39] | 25.49 (38.31), [0.10–154.01] | 0.008 | 0.013 |
HSIL-10 (pg/mL) | 1.41 (2.84), [0.14–12.17] | 1.03 (2.40), [0.05–16.27] | 0.597 | 0.835 |
sRAGE (pg/mL) | 146.8 (89.63), [13.38–327.40] | 232.22 (163.7), [10.8–970.00] | 0.041 | 0.046 |
SF-sVAP-1 (ng/mL) | 38.12 (22.98), [6.20–88.35] | 107.94 (41.42), [7.38–05.47] | <0.0001 | <0.0001 |
sVAP-1 (ng/mL)—serum | Not available | 482.5 (132.5), [180.6–695.6] |
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Bournazou, E.; Samuels, J.; Zhou, H.; Krasnokutsky, S.; Patel, J.; Han, T.; Bencardino, J.; Rybak, L.; Abramson, S.B.; Junker, U.; et al. Vascular Adhesion Protein-1 (VAP-1) as Predictor of Radiographic Severity in Symptomatic Knee Osteoarthritis in the New York University Cohort. Int. J. Mol. Sci. 2019, 20, 2642. https://doi.org/10.3390/ijms20112642
Bournazou E, Samuels J, Zhou H, Krasnokutsky S, Patel J, Han T, Bencardino J, Rybak L, Abramson SB, Junker U, et al. Vascular Adhesion Protein-1 (VAP-1) as Predictor of Radiographic Severity in Symptomatic Knee Osteoarthritis in the New York University Cohort. International Journal of Molecular Sciences. 2019; 20(11):2642. https://doi.org/10.3390/ijms20112642
Chicago/Turabian StyleBournazou, Eirini, Jonathan Samuels, Hua Zhou, Svetlana Krasnokutsky, Jyoti Patel, Tianzhen Han, Jenny Bencardino, Leon Rybak, Steven B. Abramson, Uwe Junker, and et al. 2019. "Vascular Adhesion Protein-1 (VAP-1) as Predictor of Radiographic Severity in Symptomatic Knee Osteoarthritis in the New York University Cohort" International Journal of Molecular Sciences 20, no. 11: 2642. https://doi.org/10.3390/ijms20112642